When acoustic waves, e.g., pulses of diagnostic ultrasound, propagate through a medium, e.g., tissue, absorption and scattering of the wave induce a net force, called a radiation force, in the medium. This force displaces the medium from its equilibrium position. A relatively new family of imaging methods makes use of this effect to obtain qualitatively new types of diagnostic information. Termed Acoustic Radiation Force Impulse imaging, or ARFI, the radiation force produced in tissue by long, relatively high-amplitude pulses produces tissue displacements that are quite different from those produced by standard imaging, and the magnitude and temporal dynamics of the displacements provide information on the viscoelastic properties of the tissue. These techniques allow the clinician to distinguish healthy from damaged or diseased tissue. However, ARFI employs ultrasound pulses that are much longer, and often of higher amplitude, than those currently used for ultrasound imaging, and there is concern that because these longer pulses do not adhere to the fundamental assumptions underlying the current ultrasound safety indices, i.e., the thermal index (TI) and the mechanical index (MI), ARFI may be unsafe in certain circumstances. There is a growing need for national and international standards to ensure patient safety during ARFI imaging. At present, there are few objective data upon which to base these needed standards. The goal of the proposed research project is to provide for the creation of encompassing yet flexible safety standards by conducting several series of computational and experimental studies specifically designed to acquire the data needed to develop such standards. The Specific Aims of the proposed project are: 1) determine the threshold for inertial cavitation for spherical bubbles under all relevant conditions (6 conditions have been identified, e.g., threshold criteria appropriate for mechanical in addition to thermal damage, use of longer acoustic pulse durations and dual-frequency exposures, etc.), 2) determine the temperature-time profiles and thermal doses (TD) for ARFI-type pulses (development of safety standards based on use of the thermal dose, rather than the maximum steady-state temperature rise as is currently done, is fundamental to this proposal), and 3) quantify the thermal dose in terms of absorbed energy rather than time and develop this new formulation into a universally applicable ultrasound dose metric (first following a development path like that successfully employed with ionizing radiation, then investigating a newly formulated concept, the thermal action function, which is analogous to the action integral of classical mechanics). The first two aims are relatively focused in that they will provide data to support the use of new imaging modalities. The third aim focuses on developing an exposure metric to guide selection of optimal parameters for both diagnostic and therapeutic procedures using clinical ultrasound.